Table 3.
Duration of Smoking Cessation and Colorectal Cancer Risk by Combined Molecular Subtypesa in the Nurses' Health Study (1980–2008) and the Health Professionals Follow-up Study (1986–2008)
| Current Smoker |
Cessation for 1–4 Years |
Cessation for 5–9 Years |
Cessation for ≥10 Years |
Ptrendb | |||||
|---|---|---|---|---|---|---|---|---|---|
| HR | 95% CI | HR | 95% CI | HR | 95% CI | HR | 95% CI | ||
| CIMP/MSI Subtyping | |||||||||
| CIMP-low/negative | |||||||||
| MSS | |||||||||
| No. | 94 | 37 | 60 | 346 | |||||
| Age-adjusted | 1.00 | Referent | 0.88 | 0.60, 1.29 | 1.37 | 0.99, 1.90 | 1.02 | 0.80, 1.29 | 0.66 |
| Multivariatec | 1.00 | Referent | 0.88 | 0.60, 1.29 | 1.37 | 0.99, 1.90 | 1.03 | 0.81, 1.30 | 0.81 |
| MSI-high | |||||||||
| No. | 6 | 3 | 2 | 13 | |||||
| Age-adjusted | 1.00 | Referent | 1.13 | 0.28, 4.59 | 0.71 | 0.14, 3.56 | 0.57 | 0.21, 1.56 | 0.08 |
| Multivariatec | 1.00 | Referent | 1.15 | 0.28, 4.68 | 0.70 | 0.14, 3.52 | 0.58 | 0.21, 1.58 | 0.08 |
| CIMP-high | |||||||||
| MSS | |||||||||
| No. | 11 | 2 | 3 | 19 | |||||
| Age-adjusted | 1.00 | Referent | 0.45 | 0.10, 2.05 | 0.52 | 0.14, 1.88 | 0.37 | 0.17, 0.80 | 0.02 |
| Multivariatec | 1.00 | Referent | 0.47 | 0.10, 2.14 | 0.54 | 0.15, 1.94 | 0.38 | 0.18, 0.83 | 0.02 |
| MSI-high | |||||||||
| No. | 20 | 13 | 12 | 50 | |||||
| Age-adjusted | 1.00 | Referent | 1.40 | 0.69, 2.82 | 1.08 | 0.52, 2.22 | 0.56 | 0.33, 0.96 | 0.002 |
| Multivariatec | 1.00 | Referent | 1.43 | 0.71, 2.88 | 1.07 | 0.52, 2.20 | 0.57 | 0.33, 0.97 | 0.003 |
| CIMP/DNMT3B Subtyping | |||||||||
| CIMP-low/negative | |||||||||
| DNMT3B-negative | |||||||||
| No. | 56 | 27 | 32 | 206 | |||||
| Age-adjusted | 1.00 | Referent | 1.10 | 0.69, 1.75 | 1.27 | 0.82, 1.97 | 1.25 | 0.92, 1.69 | 0.28 |
| Multivariatec | 1.00 | Referent | 1.10 | 0.69, 1.75 | 1.28 | 0.82, 1.98 | 1.27 | 0.93, 1.73 | 0.20 |
| DNMT3B-positive | |||||||||
| No. | 10 | 2 | 6 | 19 | |||||
| Age-adjusted | 1.00 | Referent | 0.52 | 0.11, 2.41 | 1.33 | 0.48, 3.70 | 0.55 | 0.25, 1.22 | 0.06 |
| Multivariatec | 1.00 | Referent | 0.53 | 0.11, 2.44 | 1.32 | 0.47, 3.69 | 0.56 | 0.25, 1.25 | 0.07 |
| CIMP-high | |||||||||
| DNMT3B-negative | |||||||||
| No. | 14 | 6 | 3 | 21 | |||||
| Age-adjusted | 1.00 | Referent | 0.95 | 0.36, 2.49 | 0.40 | 0.12, 1.41 | 0.41 | 0.20, 0.82 | 0.02 |
| Multivariatec | 1.00 | Referent | 0.98 | 0.37, 2.57 | 0.41 | 0.12, 1.42 | 0.42 | 0.21, 0.85 | 0.02 |
| DNMT3B-positive | |||||||||
| No. | 7 | 3 | 2 | 7 | |||||
| Age-adjusted | 1.00 | Referent | 1.07 | 0.27, 4.17 | 0.55 | 0.11, 2.67 | 0.28 | 0.10, 0.81 | 0.01 |
| Multivariatec | 1.00 | Referent | 1.12 | 0.29, 4.38 | 0.56 | 0.12, 2.73 | 0.29 | 0.10, 0.85 | 0.01 |
Abbreviations: CI, confidence interval; CIMP, CpG island methylator phenotype; DNMT3B, DNA methyltransferase 3B; HR, hazard ratio; MSI, microsatellite instability; MSS, microsatellite stable.
a All models were stratified by calendar year of the questionnaire cycle, age, and sex.
b Based on the linear trend test by using the median value of each category. To test whether the duration of smoking cessation reduced the cancer risk compared with current smoking, trend test and heterogeneity tests were performed on current and past smokers, excluding never smokers.
c Models were adjusted for body mass index, family history of colorectal cancer in any first-degree relative, regular use of aspirin, physical activity level, alcohol consumption, total caloric intake, and red meat intake.